Improving Bioluminescent Test for PSA

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CBST researchers at Stanford University, Lawrence Livermore National Laboratory, and UC Davis are developing a more robust in vitro diagnostic assay for serum protease activity, which could potentially lead to a more sensitive and reliable test for prostate cancer.

Fireflies produce bioluminescent light through the reaction of the luciferase enzyme with the small molecule luciferin substrate (colored). Synthetic chemists at LLNL and UC Davis have modified the luciferin molecule by adding a short peptide chain (shown in black) that blocks the bioluminescent reaction. By selecting a peptide sequence that is recognized and cleaved by a specific proteolytic enzyme, bioluminescence can once again occur -- indicating the presence and activity of the targeted protease.

CBST researchers have made a prototype assay for prostate specific antigen (PSA), which is a protease enzyme and a marker that is linked to prostate cancer. Bioluminescent detection of PSA is effectively 1000 times more sensitive than the currently used fluorescent antibody based tests, and because this type of assay is sensitive only to protease activity, it is expected to be better correlated to the presence of cancer.